In a pending U.S. patent application bearing Ser. No. 12/545,172, this inventor disclosed a wearable personal communication device based method of non-pharmaceutical prescription that administers, monitors, measures and motivates a therapeutic lifestyle regimen for improving prevention, treatment and prognosis of chronic diseases. The '668 disclosure termed Rx-Zero teaches not only the prevention component by eliminating the need for pharmaceutical interventions, but also includes the therapy component after the chronic disease has actually been diagnosed. In the former the disease onset is prevented before it sets in, while in the later situation it targets the lifelong drug usage to minimal or zero by deploying the lifestyle changes as the first line of treatment, and prescription drugs only to supplement and support the first line of treatment.
Although the '668 Rx-Zero disclosure measured and monitored the therapeutic dose of physical activity prescribed and its impact on health in general it did not consider other parameters that may be implicated in optimizing the doses of physical activity to maximize the gains of revascularization interventions and minimize the post procedure restenosis complications in everyday interventional cardiology practice. To fill that gap this inventor, in another application, disclosed a method and apparatus that enables prescription, administration and monitoring compliance of a measured therapeutic or rehabilitative optimal myocardial stress induction (OMSI) regimen for complimenting a coronary revascularization intervention to prevent/reduce the post-procedure restenosis risk. In continuation of the concept of non-pharmacological intervention for management of morbidities the instant invention exploits another naturally occurring phenomenon of remote ischemic preconditioning for preventing subsequent ischemia-reperfusion injury, or improving vascular functions of patient with chronic cardiovascular disease. The instant invention discloses an apparatus to harness the innate power of transient ischemia in preparing the body for better defense against ischemic, ischemia-reperfusion, or any other physiological or pathological insults to organs.
Ischemia-reperfusion injuries are implicated in a large array of pathological conditions such as myocardial infarction, cerebral stroke, and hepatic, renal or lung transplant, etc. Unfortunately such ischemia-reperfusion injuries are still considered as an inevitable price the patient has to pay for the surgical intervention. Most patients who undergo revascularization of blocked coronary arteries end up with larger size infarct (dead myocardium) then that caused by the blockage itself, merely because of the revascularization procedure undertaken to open up the blockages and salvage the myocardium. It is a paradox that the procedure that aims to perfuse and salvage the myocardium kills more of it in the process. Moreover, almost all of the patients undergoing balloon catheterization face long term effects of ischemia-reperfusion injury caused during ballooning and stenting. Such long term effects include increased risk of restenosis and future cardiovascular events.
While the benefit of an improved perfusion of the myocardium is certainly desirable, nevertheless the cost of an increased infarct size is indeed a very high price to pay. The actual annual cost of ischemia-reperfusion injury to mankind therefore is humongous and incalculable considering millions of such high reperfusion injury risk procedures are performed globally on a daily basis. While lethal reperfusion injury remains the next major target for the treatment of patients with acute myocardial infarction and coronary revascularization, many other surgical settings such as organ transplant, protracted procedures requiring clamping of blood supply to an organ remain ridden with the ischemia-reperfusion injury problem. There are no current solutions on the market to address this huge problem.
Transient tissue hypoxia/ischemia is one of the most potent physiological triggers of systemic protection against subsequent ischemia-reperfusion related damage to the organs. It is the most potent innate mechanism of protection that can be induced in our tissues. Yet ischemia-reperfusion injury to organs remains the most commonly acknowledged risk of surgical intervention in the practice of modern medicine. In their 1986 seminal paper Murray et al for the first time reported this natural ischemic pre-conditioning phenomenon (Murray C E, et al. Circulation 1986; 74 (5): 1124-36). Subsequently it was demonstrated in a canine model that brief episodes of ischemia in one myocardial vascular bed, protects remote virgin myocardium from a sustained coronary artery occlusion feeding another vascular bed implying that preconditioning may be mediated by factors activated, produced, or transported throughout the heart during brief ischemia/reperfusion (Przyklenk K, et al. Circulation. 1993; 87(3):893-9). However, only in the preceding few years there has been a flurry of reports discovering that the ischemic preconditioning can be easily induced systemically with a remote stimulus, without having to access the target organ itself (Ali Z A et al. Circulation. 2007 Sep. 11; 116(11 Suppl: I98-105; Venugopal V et al. Eur. J. Cardiothorac. Surg. 2009; 35:977-987; Kharbanda R K et al. The Lancet, 2009; Vol 374: 9700, 1557-1565, 31). The knowledge that transient intermittent ischemia in limbs can remotely induce ischemic preconditioning in the entire body is fast changing the landscape of ischemia-reperfusion injury.
Recent clinical studies emphasize that lethal reperfusion injury represents a large amount of the overall myocardial damage after acute myocardial infarction, and have shown that ischemic preconditioning substantially reduces infarct size, and that this tissue destruction during surgical procedures such as coronary revascularization can be prevented by a timely intervention with remote ischemic preconditioning (Ovize M & Bonnefoy E. The Lancet, 2010; Vol 375:9716, 699-700, 27). Although ischemic preconditioning has been largely studied more extensively in the context of myocardial damage, there are reports of similar beneficial effects on almost any organ of the body.
For example Dembinski A et al showed that ischemic pre-conditioning, applied prior to ischemia-reperfusion-induced pancreatitis, strongly reduces the severity of acute pancreatitis via reduction in plasma lipase activity and a decrease in plasma concentration of pro-inflammatory interleukin-18, and increase in plasma concentration of anti-inflammatory interleukin-10, improvement in pancreatic blood flow and increased expression of PDGF-A and VEGF (Dembinski et al. Physiol Pharmacol 2006; 57(1):39-58). Nikeghbalian et al subsequently showed the ischemic preconditioning of liver protected pancreas from ischemia-reperfusion injury (Nikeghbalian S, et al. Saudi J Kidney Dis Transpl 2009; 20:1010-4).
Botker et al very recently reported a randomized study in which arm ischemia (induced by four cycles of alternating 5-min inflation and 5-min deflation of a standard upper-arm blood-pressure cuff) significantly increased myocardial salvage in 142 patients with ST-elevation acute myocardial infarction (STEM) (Botker H E, et al. The Lancet, 2010; Vol 375:9716, 727-734, 27).
Remote ischemic preconditioning, as is emerging today, may appear easy to deliver through a straightforward procedure such as intermittent ischemia of the upper or lower limb, induced by inflating and holding a blood-pressure cuff above the patient's systolic blood pressure. It has no known adverse risks and in the published clinical studies the technique is executed using a manual auscultatory sphygmomanometer. The ability to use the manually inflating blood pressure cuff, albeit with obvious inconvenience of a continuous hour long doctor/nurse-in-attendance procedure, is predicted as the downfall of this otherwise low-tech technique. Its non-pharmacological nature is also feared to preclude sponsorship from the pharmaceutical industry.
The currently available automatic sphygmomanometers use a self-inflating cuff to exert controlled counter-pressure on the vasculature of a patient. In typical automatic sphygmomanometric devices, the cuff deflation operation is accomplished in equal decrements, usually about 8 mm Hg per step. They are not designed to hold pressure for an extended duration and cannot cycle between ischemic and reperfusion durations as may be required when remote ischemic preconditioning is performed on patients. As such, only manually inflatable blood pressure measuring systems can be used. But such systems require the presence of a medical professional throughout the procedure that may take over an hour to complete. Remote ischemic preconditioning protocols may also vary extensively from patient to patient or even from treatment to treatment for a given patient, which may cause confusion among those that administer the treatment. Such procedure is therefore impractical in an emergency when the patient is being transferred to the hospital for treatment. It is also is impractical for a cardiologist to spend an hour on the procedure when the actual angioplasty may take even lesser time. It is also impractical if the ischemic preconditioning is prescribed to a home-based ambulatory patient on a regular basis.
Therefore there is urgent need to solve all of these problems and accomplish the entire procedure of prescribing, administering, monitoring and measuring and optimizing the ischemic preconditioning regimen with a single touch use friendly device requiring very little of the physician time or with his remote supervision of the treatment protocol.